Wettable ePTFE Medical Devices

ABSTRACT

Methods are provided for surface modifying a hydrophobic polymer substrate to increase wettability comprising the steps of pre-treating the hydrophobic polymer substrate with a radio frequency (RF)-generated first plasma and a RF-generated second plasma wherein the first plasma and the second plasma are applied sequentially, coating the hydrophobic polymer substrate with a hydrophilic coating; and polymerizing the hydrophilic coating on the hydrophobic polymer substrate by exposure to a RF-generated third plasma.

CROSS REFERENCE TO RELATED APPLICATIONS

This is a divisional application and claims priority to U.S. applicationSer. No. 11/742,433 filed Apr. 30, 2007 which claims priority to U.S.Provisional Application No. 601795,668 filed Apr. 28, 2006, the entirecontents of which is incorporated by reference herein.

FIELD OF THE INVENTION

The present invention relates to surface modification of expandedpolytetrafluoroethylene substrates to enhance hydrophilicity and,therefore, wettability.

BACKGROUND OF THE INVENTION

Implantable medical devices have become increasingly more common overthe last 50 years and have found applications in nearly every branch ofmedicine. Examples include joint replacements, vascular grafts, heartvalves, ocular lenses, pacemakers, vascular stents, urethral stents, andmany others. However, regardless of the application, implantable medicaldevices must be biocompatible, that is, they must be fabricated frommaterials that will not elicit an adverse biological response such as,but not limited to, inflammation, thrombogenesis or necrosis. Thus,early medical devices were generally fabricated from inert materialssuch as precious metals and ceramics. More recently, stainless steel andother metal alloys have replaced precious metals and polymers are beingsubstituted for ceramics.

Polytetrafluoroetheylene (PTFE) is a polymer comprised of carbon chainssaturated with fluorine. The use of PTFE in medical applications beganin the construction of artificial heart valves. Expanded PTFE is porous,biostable, and implantable medical devices made from it do not degradewithin the body.

Expanded polytetrafluoroethylene materials are now widely used in avariety of medical devices; for example, vascular grafts, ablationcatheters, etc.

Expanded polytetraflouroethylene offers many advantageous physicalproperties relating to medical devices. Along with a low coefficient offriction, ePTFE is biocompatible, chemically resistant, linearly strong,UV resistant, waterproof, flexible, etc. However, ePTFE is extremelyhydrophobic and not easily wettable. Medical devices made of ePTFE arenon-wetting when introduced into an aqueous environment, limiting theiruse in certain applications.

Therefore, methods to decrease hydrophobicity, and therefore improvewettability, of ePTFE medical devices are needed to optimize thesedevices.

SUMMARY OF THE INVENTION

The present invention provides methods to render hydrophobic polymerswettable. In one embodiment of the present invention, expandedpolytetrafluoroethylene (ePTFE) is surface modified with hydrophilicagents, thereby decreasing its hydrophobicity and improving itswettability. More specifically, ePTFE materials are pre-treated withplasma to activate the surface, exposed to a hydrophilic polymer andtreated again with a plasma to crosslink the hydrophilic coating on theePTFE surface.

In one embodiment of the present invention, a method of surfacemodifying a hydrophobic polymer substrate to increase wettability isprovided comprising pre-treating a hydrophobic polymer substrate with aradio frequency (RF)-generated first plasma and a RF-generated secondplasma wherein the first plasma and the second plasma are appliedsequentially, coating the hydrophobic polymer substrate with ahydrophilic coating, and polymerizing the hydrophilic coating on thehydrophobic polymer substrate by exposure to a RF-generated thirdplasma.

In another embodiment of the present invention, the hydrophobic polymersubstrate comprises an expanded polytetrafluoroethylene (ePTFE)substrate.

In another embodiment, the first RF-generated plasma comprises an inertgas plasma. In another embodiment, the inert gas plasma is an argonplasma.

In another embodiment of the present invention, the second RF-generatedplasma is a reactive gas plasma. In another embodiment the reactive gasplasma is an H₂O plasma.

In one embodiment of the present invention, a method of surfacemodifying an ePTFE substrate to increase wettability is providedcomprising pre-treating the ePTFE substrate with a radio frequency(RF)-generated argon plasma and a RF-generated H₂O plasma wherein theargon plasma and the H₂O plasma are applied sequentially; coating theePTFE substrate with a PEG-acrylate coating; and polymerizing thePEG-acrylate coating on the ePTFE substrate by exposure to aRF-generated argon plasma.

In yet another embodiment of the present invention, the hydrophiliccoating comprises a polyethylene glycol acrylate (PEG-acrylate) polymerhaving the general structure H₂C=CHCO(OCH₂CH₂)_(n)OH, wherein n is aninteger between 1 and 300. In another embodiment, n is 200.

In another embodiment of the present invention, the coating stepcomprises exposing the hydrophobic polymer substrate to a solution ofPEG-acrylate in methanol wherein the concentration of PEG-acrylate isapproximately 5% to approximately 95%. In another embodiment, theconcentration of PEG-acrylate in the solution is approximately 15% toapproximately 25% by weight.

In an embodiment of the present invention, the ePTFE substrate comprisesan ePTFE medical device selected from the group consisting ofreplacement joints, tubing, vascular grafts, catheters, heart valves,ocular lenses, pacemakers, pacemaker leads and stents. In anotherembodiment; the ePTFE medical device comprises an vascular graft. In yetanother embodiment of the present invention, the ePTFE medical devicecomprises an ablation catheter.

In one embodiment of the present invention, a medical device is providedcomprising ePTFE wherein the medical device has a PEG-acrylate coatingon at least a portion of the medical device surface, the coatingdeposited by exposure to at least one RF-generated plasma. In anotherembodiment, the medical device is selected from the group consisting ofreplacement joints, tubing, vascular grafts, catheters, heart valves,ocular lenses, pacemakers, pacemaker leads and stents. In yet anotherembodiment, the PEG-acrylate has the general structureH₂C=CHCO(OCH₂CH₂)_(n)OH, wherein n is an integer between 1 and 300.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 graphically depicts one embodiment of the method to surfacemodify expanded polytetrafluoroethylene (ePTFE) according to theteachings of the present invention.

FIG. 2 depicts high resolution C1s X-ray photoelectron spectroscopy(XPS) spectral analysis of untreated ePTFE (FIG. 2A) andplasma/polyethylene glycol (PEG)-acrylate coated ePTFE (FIG. 2B)according to the teachings of the present invention. OD=outer surface;ID=inner surface.

FIG. 3 depicts scanning electron microscope images of untreated ePTFE(FIG. 3A, 800×) and the outer surface of plasma treated/PEG-acrylatecoated ePTFE (FIG. 3B, 1000×) according to the teachings of the presentinvention.

FIG. 4 depicts untreated ePTFE tubing and plasma-treated ePTFE tubingcoated with PEG-acrylate by the vacuum assisted technique according tothe teachings of the present invention. Both samples have been stainedwith toluidine blue dye.

FIG. 5 depicts scanning electron microscopy images of outer (FIGS. 5Aand 5C) and inner surfaces (FIGS. 5B and 5D) of plasma-treated andvacuum-grafted PEG-acrylate coated ePTFE (FIG. 5C and 5D) and uncoatedePTFE control (FIG. 5A and 5B) according to the teachings of the presentinvention.

DEFINITION OF TERMS

Generally, all technical terms or phrases appearing herein are used asone skilled in the art would understand to be their ordinary meaning.For the convenience of the reader, however, selected terms are morespecifically defined as follows.

Biocompatible: As used herein, “biocompatible” shall mean any materialthat does not cause injury or death to the animal or induce an adversereaction in an animal when placed in intimate contact with the animal'stissues. Adverse reactions include inflammation, infection, fibrotictissue formation, cell death, or thrombosis.

Contact Angle: As used herein, the “contact angle” is the angle at whicha liquid interface meets the solid surface and is a measure ofwettability. The contact angle is indicated by the symbol θ. The contactangle is specific for any given system and is determined by theinteraction between the solid, the liquid and vapor phases.

ePTFE: As used herein, “ePTFE” is an acronym for expandedpolytetraflouroethylene. Expanded PTFE material is obtained by expandingPTFE (polytetraflouroethylene) material under controlled conditionsduring the manufacturing process. This process alters the physicalproperties of the material by creating microscopic pores in thestructure of the material.

Hydrophilic: As used herein, the term “hydrophilic” refers to a materialthat has a high affinity for or even attracts water. The phenomenon istypically due to a predominance of polar molecules in the material, butmay be caused by other factors. When referring to a solid, hydrophilicmeans the material has more hydrophilic matter than hydrophobic matterat least at its surface. Hydrophilic materials are readily wettable bywater.

Hydrophobic: As used herein, the term “hydrophobic” refers to a materialthat has low or no affinity for or even repels water. The phenomenon istypically due to a predominance of non-polar molecules in the material,but may be caused by other factors. When referring to a solid,hydrophobic means the material has more hydrophobic matter thanhydrophilic matter at least at its surface. Hydrophobic materials arenot substantially wettable by water.

Inert Gas: As used herein, “inert gas” refers to a noble gas includingthe chemical elements in group 18 (old-style Group 0) of the periodictable. This chemical series contains helium, neon, argon, krypton, xenonand radon.

Plasma: As used herein, “plasma” refers to conductive assemblies ofcharged particles, neutrals and fields that exhibit collective effects.Further, plasmas carry electrical currents and generate magnetic fields.Moreover, plasma consists of a collection of free moving electrons andions (atoms or molecules that have lost electrons). Energy is needed tostrip electrons from atoms or molecules to make the plasma. The energycan be of various origins: thermal, electrical, or light (ultravioletlight or intense visible light from a laser). With insufficientsustaining power, plasmas recombine into neutral gas. Electrical powercan be applied at different frequencies, such as, but not limited to,radiofrequencies and microwaves. Plasma can be accelerated and steeredby electro-magnetic fields, which allows it to be controlled andapplied.

Process pressure: As used herein, “process pressure” refers to theplasma reactor chamber pressure during plasma treatment as measured inmTorr. Generally, process pressure is less than standard atmosphericpressure so there is at least a partial vacuum present in the chamber(less than normal atmospheric pressure, 760 Torr or 14.7 psi). However,process pressures may be greater than 760 Torr.

Reactive Gas: As used herein, “reactive gas” refers to all other gasesnot defined as inert gas.

Substrate: As used herein, “substrate” refers to hydrophobic polymermaterials, including, but not limited to, films, fabrics, membranes,tubing and medical devices.

Wet coating: As used herein, “wet coating” refers to dipping a substrateinto a solution to coat the substrate.

Vacuum-assisted wet coating: As used herein, “vacuum-assisted wetcoating” refers to a method of wet coating a substrate by removing allentrapped gaseous bubbles from the surfaces of the substrate with avacuum

Wettable or Wettability: As used herein, “wettable” or “wettability”refers to the ability of a solid to be covered, soaked, or dampened withwater or some other liquid. Wettability is determined by thermodynamicproperties, such as surface energy and surface tension. Wettability ismeasured by contact angle (θ) formed at the three phase contact point ofa drop of liquid with a solid surface (spreading or wicking into porousmaterial). A material is determined to be completely wettable if thecontact angle is 0°. A contact angle of <90° indicates partial wettingand a contact angle of >90° indicates a non-wetting surface

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides methods for modifying the hydrophobicsurfaces of medical devices to render them wettable while maintainingthe structural integrity and functionality of the medical device.Additionally, the medical devices of the present invention have a welladhered hydrophilic coating on luminal and exterior surfaces.

Expanded polytetrafluoroethylene (ePTFE) is a hydrophobic polymermaterial often used in medical devices because it is chemically stable,physically robust, biologically inert, microporous, non-toxic andbiocompatible. However, a main disadvantage of ePTFE is its highhydrophobicity, therefore ePTFE medical devices and substrates areresistant to wetting.

Surface modification of ePTFE, to render it more wettable, can beaccomplished by chemical methods including wet chemical modification,plasma treatment processes or a combination of the two. For example,ablation catheters are pre-wetted with alcohol before use to enhancetheir wettability in an aqueous environment. Methods which can yieldstable, wettable ePTFE surfaces are needed.

Expanded polytetrafluoroethylene-containing medical devices that maybenefit from modification to increase wettability include, but notlimited to, vascular grafts, stent grafts, blood filter membranes,tubing, catheters, pacing electrodes, cell isolation devices, stents,replacement joints, pacemakers, ocular lenses and sensors. Exemplarycatheters include, but are not limited to, ablation catheters. Exemplarystents include, but are not limited to, vascular stents, biliary stentsand urethral stents.

The present invention provides methods for the surface modification ofePTFE surfaces using a multi-step process involving radio frequency(RF)-generated plasmas. In one embodiment of the present invention, amethod is provided for surface modifying ePTFE by 1) RF plasmapre-treatment; 2) wet coating the ePTFE surface with a hydrophilic agentand 3) RF plasma post-treatment to crosslink the hydrophilic agent onthe ePTFE surface (FIG. 1).

In one embodiment of the present invention, the first step comprisespre-treating the surface of a hydrophobic ePTFE substrate by exposure toat least one RF-generated plasma. Radio frequency-generated plasmassuitable for use in the first step of the method of the presentinvention include, but are not limited to, inert and reactive gasplasmas, or combinations thereof. Reactive gases useful for treating thesurface of PTFE materials include, but are not limited to O₂, N₂, NH₃,H₂S, H₂O, CO, CO₂, SO₂, SO₃, N₂O and HN₃. Inert gases useful in themethods of the present invention include, but are not limited to, argon,helium, neon, krypton, xenon and radon. In one embodiment of the presentinvention, the pre-treatment RF-generated plasma is argon plasma. Inanother embodiment, the pre-treatment RF-generated plasma is H₂O plasma.In yet another embodiment, the pre-treatment RF-generated plasmacomprises both argon plasma and H₂O plasma, applied sequentially. Inertgas plasmas produce a roughened, activated surface on the ePTFEsubstrate. Reactive gas plasmas functionalize the ePTFE substrate. Forexample, and not intended as a limitation, treatment of the ePTFEpolymer with H₂O plasma introduces oxygen-containing carbon functionalgroups onto the surface of the ePTFE substrate. At this stage the ePTFEsurface is prepared to accept a hydrophilic coating.

In an embodiment of the methods of the present invention, the secondstep comprises wet coating the ePTFE surface with a hydrophilicmaterial. The wet coating is accomplished by methods known to persons ofordinary skill in the art including, but not limited to, dipping andvacuum-assisted wet chemical coating. Vacuum-assisted wet chemicalcoating is a process wherein a vacuum is applied to a chamber thatcontains the ePTFE substrate in a solution of the hydrophilic material.The vacuum removes the air bubbles on the porous ePTFE surfaces andforces the hydrophilic material into the pore spaces resulting incoating of the exposed surfaces. Entrapped air bubbles in the porousePTFE substrate can inhibit performance and yield a non-uniform coating.In one embodiment of the present invention, the hydrophilic material isdissolved in an appropriate solvent, in a non-limiting example,methanol, at a concentration of between 5% and 95%. In anotherembodiment, the hydrophilic material is present in the solution at aconcentration between 10% and 75%. In another embodiment, thehydrophilic material is present in the solution at a concentrationbetween 12% and 50%. In another embodiment, the hydrophilic material ispresent in the solution at a concentration between 15% and 25%. Inanother embodiment, the hydrophilic material is present in the solutionat a concentration of 20%.

Exemplary hydrophilic materials include, but are not limited topolysaccharides, polyols, polyethylene glycol (PEG) and PEG-acrylatepolymers.

Polyethylene glycol acrylate polymers useful as hydrophilic coatings inthe methods of the present invention include polymers of the generalstructure (Formula 1), wherein n is an integer between about 1 and about300.

In one embodiment of the present invention, n is an integer betweenabout 50 and about 275. In another embodiment, n is an integer betweenabout 100 and about 250. In another embodiment, n is an integer betweenabout 150 and about 225. In another embodiment, n is an integer of about200.

In another embodiment of the present invention, the hydrophilic materialused to coat the pre-treated ePTFE surface is an organic acid such as,but not limited to, acetic acid. In another embodiment of the presentinvention, the hydrophilic material used to coat the pre-treated ePTFEsurface is a polyol such as, but not limited to, glycerol.

In another embodiment of the present invention, the third step comprisespolymerizing the hydrophilic material on the ePTFE surface by exposureto RF-generated plasma. RF-generated plasmas suitable for polymerizingthe hydrophilic materials include, but are not limited to, inert gasplasmas such as argon.

The RF-generated plasma pre-treatment and polymerizing processes areconducted in a closed environment at process pressures of about 10 mTorrto about 200 mTorr. In one embodiment of the present invention, processpressures are from about 10 mTorr to about 100 mTorr. In anotherembodiment, process pressures are from about 20 mTorr to about 50 mTorr.In another embodiment, process pressure is about 100 mTorr. In oneembodiment, process pressure is about 25 mTorr.

The power for generating plasmas can vary depending upon treatmentapplications. The power for the generation of the RF (13.56 MHz) plasmaranges from about 15 W to about 500 W. In one embodiment of the presentinvention, the power ranges from about 15 W to about 500 W. In anotherembodiment, the power ranges from about 20 W to about 400 W. In anotherembodiment, the power ranges from about 30 W to about 300 W. In anotherembodiment, the power ranges form about 40 W to about 200 W. In anotherembodiment, the power ranges from 50 W to about 100 W.

Gas flows in the generation of plasma comprise various volumetric rates.Gas flow in the plasma chamber ranges from about 0.5 sccm (standardcubic centimeter per minute) to about 40 sccm. In one embodiment of thepresent invention, gas flow in the plasma chamber ranges from about 0.5sccm to about 40 sccm. In another embodiment, gas flow in the plasmachamber ranges from about 0.6 sccm to about 30 sccm. In anotherembodiment, gas flow in the plasma chamber ranges from about 0.7 sccm toabout 25 sccm. In another embodiment, gas flow in the plasma chamberranges from about 0.8 sccm to about 20 scam In another embodiment, gasflow in the plasma chamber ranges from about 0.9 sccm to about 15 sccm.In another embodiment, gas flow in the plasma chamber ranges from about1 sccm to about 10 sccm. In another embodiment, gas flow in the plasmachamber ranges from about 2 sccm to about 5 sccm.

Various excitation frequencies are also chosen to generate plasma. Inone embodiment of the present invention, a frequency of 13.56 MHz isused to generate plasma. In another embodiment, multiples of 13.56 MHzare used to generate plasma e.g. 27.12 MHz (2×13.56 MHz). In yet anotherembodiment, fractions of 13.56 MHz are used to generate plasma e.g. 6.78MHz (0.5×13.56 MHz). Frequencies in the range of microwaves are alsoused. In one embodiment of the present invention 2.45 GHz is used toexcite the gas and generate plasma.

The degree of hydrophilicity of the surface of the surface modifiedePTFE materials are measured by dynamic contact angle (DCA) analysis.For any given solid/liquid interaction there exists a range of contactangles which may be found. The value of static contact angles are foundto depend on the recent history of the interaction. When the drop hasrecently expanded the angle is said to represent the ‘advanced’ contactangle. The advancing angle is defined as the angle between the surfaceof the water and the surface of the polymer upon initial wetting of thepolymer. When the drop has recently contracted the angle is said torepresent the ‘receded’ contact angle. These angles fall within a rangewith advanced angles approaching a maximum value and receded anglesapproaching a minimum value. The difference between the maximum(advancing) and minimum (receding) contact angle values is called thecontact angle hysteresis.

The advancing angle measurement is used to determine hydrophilicity. Forwettable surfaces, the advancing angle, as determined by DCA, is lessthan 90° while non-wettable surfaces have advancing angles greater than90°. A complete wetting of the polymer surface is represented by anadvancing angle of 0°. Water is used as the test liquid.

EXAMPLES Example 1

Surface Modification of ePTFE with PEG-Acrylate by Dipping

An ePTFE substrate is exposed to an argon plasma with an processpressure of 100 mTorr (225 W RF power, 10 sccm Ar) for 20 minutes. Thenthe ePTFE substrate is exposed to H₂O plasma with a process pressure of24 mTorr (200 W RF power, 5 sccm H₂O) for 10 minutes. The pre-treatedePTFE substrate is then dipped in a 20% by weight solution ofPEG-acrylate (n=200) in methanol for 1 minute. Then the wet-coated ePTFEsubstrate is exposed to argon plasma with a process pressure of 25 mTorr(25 W RF power, 10 sccm Ar) for 2 minutes. The method yields a wettableePTFE substrate as evidenced by the advancing angle of 35.69° aftertreatment compared to 99.41° for the untreated ePTFE.

Analysis of PEG-acrylate coated ePTFE substrates includes dynamiccontact angle with water for wettability, X-ray photoelectronspectroscopy (XPS), time of flight secondary ion mass spectroscopy(ToF-SIMS) to investigate surface chemistry and scanning electronmicroscopy (SEM) to evaluate the surface morphology.

The PEG-acrylate coating applied to ePTFE substrates demonstratedincreased wettability and a lower advancing angle compared to theuntreated ePTFE (Table 1). The PEG-acrylate coating combined withRF-plasma pre-coating and polymerizing steps resulted in ePTFEsubstrates with the lowest advancing angle (plasma/PEG-acrylate, Table1). Additionally, the plasma/PEG-acrylate modified ePTFE is stable overtime following storage in air and H₂O.

TABLE 1 Relative Wettability Measured by Dynamic Contact Angle AnalysisAdvancing Receding Hysteresis ePTFE treatment Angle (°) Angle (°) (°)Untreated 99.41 77.57 21.84 Plasma/PEG-acrylate coating 35.69 26.83 8.86Plasma/PEG-acrylate coating 34.38 24.96 9.42 stored in air for 2 weeksPlasma/PEG-acrylate coating stored 32.21 26.70 5.51 in H₂O for 2 weeks

Plasma processes result in the excitation of chemical species formingions and free radicals, therefore a variety of functional groups canform on the plasma-treated ePTFE substrate surface. XPS analysis of theinner and outer surfaces of surface modified ePTFE tubing demonstratedthat the surfaces of untreated ePTFE contained mostly C and F functionalgroups while the PEG-acrylate treated surfaces consisted primarily of Cand O functional groups (FIG. 2). Measured XPS atomic concentrationswere compared with theoretical atomic concentrations for the coatingbased upon the chemical formula of PEG-acrylate, n=200. Table 2 belowshows experimental and theoretical values. Theoretical percent atomicconcentrations showed good correlation to measured values.

The XPS data demonstrate presence of a coating on the inner and outersurfaces of the ePTFE tubing following plasma treatment and that thecoating retains the PEG-like structure of the monomer.

TABLE 2 Measured XPS Surface Atomic Concentrations and Calculated BulkAtomic Concentrations C O F XPS-Measured Atomic Concentrations (%)Untreated outer surface 33.4 0.5 66.1 Untreated inner surface 31.0 nd69.0 PEG-acrylate outer surface 62.5 36.0 0.6 PEG-acrylate inner surface63.0 36.0 nd Theoretical Atomic Concentrations Calculated from ChemicalStructure (%) PEG-acrylate (n = 200) 66.6 33.4 0 PTFE (CF₂—CF₂)_(n) (nis large) 33.3 0 66.7

The surfaces were also analyzed by scanning electron microscopy (SEM).SEM images indicate that the plasma and PEG coating process resulted incoating on both the nodes and fibrils of the inner and outer surfaces(FIG. 3) of the ePTFE tubing.

Example 2

Surface Modification of ePTFE Tubing with PEG-Acrylate by VacuumAssisted Wet Coating

An ePTFE substrate is exposed to argon plasma with a process pressure of100 mTorr (225 W RF power, 10 sccm Ar) for 20 minutes. Then the ePTFEsubstrate is exposed to H₂O plasma with a process pressure of 24 mTorr(200 W RF power, 5 sccm H₂O) for 10 minutes. The pre-treated ePTFEsubstrate is removed from the plasma reactor chamber and placed in acentrifuge tube in a 20% by weight solution of PEG-acrylate (n=200) inmethanol. The centrifuge tube is then placed in a beaker and enclosed inanother chamber wherein a variable vacuum is drawn thereby removing airbubbles from the ePTFE pores and forcing the PEG-acrylate solution intothe pores. The chamber is then brought up to atmospheric pressure andthe vacuum assisted wet-coated ePTFE samples are removed and placed inthe plasma reactor chamber. Then the vacuum assisted wet-coated ePTFEsubstrate is exposed to argon plasma with a process pressure of 25 mTorr(25 W RF power, 10 sccm Ar) for 2 minutes.

The wettability of plasma treated samples that were coated withPEG-acrylate by the vacuum assisted technique was assessed by stainingwith toluidine blue, a polycationic dye that stains for negative chargeor polar functional groups. Since these functional groups contribute towettability, this method was used to gauge the wettability of the porousePTFE tubing throughout the tubing walls. Untreated and coated sampleswere dipped in a 1% aqueous solution of toluidine blue for 1 minute. Thesamples were then removed and rinsed under running water for at least 3minutes or until the rinse water was colorless. The samples were allowedto dry before examining. A top view of stained untreated (left) andstained coated (right) samples is shown in a photograph in FIG. 4. Thesurface of the uncoated sample remained white after staining, suggestingthat the dye did not attach to the ePTFE surface. The PEG-acrylatecoated sample stained dark blue, indicating that the dye had attached tonegative/polar functional groups in the PEG coating. Additionally, thisblue color extended throughout the porous walls of the ePTFE tubing.This suggested that the PEG-acrylate coating had penetrated the poresand coated the pore walls and that the pore spaces within the samplewere wettable.

FIG. 5 depicts SEM images of outer (FIGS. 5A and 5C) and inner surfaces(FIGS. 5B and 5D) of plasma-treated and vacuum grafted PEG-acrylatecoated ePTFE (FIG. 5C and 5D) and uncoated ePTFE control (FIG. 5A and5B).

Example 3

Surface Modification of ePTFE with PEG-Acrylate by Dipping and DifferentPlasma Parameters

Different batches of samples were made following the basic procedure ofAr plasma pretreatment, H₂O plasma treatment, dipping in PEG-acrylateand Ar plasma post-treatment. Ar and H₂O plasma treatment variables werevaried as shown in Table 3. Additionally, for the Ar plasma treatment Arflow was held constant at 10 sccm. For the H₂O plasma treatment thepressure was held to 24 mTorr and the H₂O flow rate was 5 sccm. Afterboth plasma treatments, the pre-treated ePTFE substrate was dipped in a20% by weight solution of PEG-acrylate (n=200) in methanol for 1 minute.Then, the wet-coated ePTFE substrate was exposed to Ar plasma with aprocess pressure of 25 mTorr (25 W RF power, 10 sccm Ar) for 2 minutes

TABLE 3 Plasma processing variables for Ar and H₂O plasmapre-treatments. Ar Pre-treatment H₂O Pre-Treatment Sample Ar Pressure ArPower Ar Time H₂O power H₂O Time Batch (mTorr) (Watts) (min) (Watts)(min) 2 100 200 10.0 200 5.0 4 100 100 20.0 200 5.0 5 50 200 20.0 2005.0 7 50 200 10.0 100 5.0 8 50 200 20.0 100 10.0

The PEG-acrylate coated ePTFE materials processed under these conditionsdemonstrated durable wettability. Table 4 shows the water contact anglesof various batches of samples measured initially, after aging in air andaging in buffer on a shaker table. The changes in the advancing anglesafter aging the PEG-acrylate coated ePTFE substrate in air are minimal(0° to10°). With additional aging in phosphate buffered saline (PBS)solution under dynamic conditions at 37° C., the advancing contact angleincreases about 15° to 25°. However, the surface still retains improvedwettability compared to the untreated ePTFE material (advancing contactangle=110.19°).

TABLE 4 Stability of Plasma/PEG-acrylate modified ePTFE surfaces withaging in air and in PBS solution. Advancing Angle (°) Receding Angle (°)2 mo aging 2 mo aging 2 mo aging in air + 2 2 mo aging in air + 2 BatchInitial in air wks in PBS Initial in air wks in PBS Untreated 119.02 ±2.82  118.78 ± 2.23  110.19 ± 3.02  88.87 ± 2.52 93.69 ± 1.57 60.77 ±7.44 ePTFE 2 41.17 ± 3.35 45.86 ± 2.76 62.71 ± 5.12 32.97 ± 1.79 31.45 ±2.82 35.38 ± 4.34 4 39.33 ± 2.82 37.44 ± 8.32 63.43 ± 5.44 32.31 ± 2.5225.07 ± 4.79 39.80 ± 3.06 5 37.40 ± 1.69 43.84 ± 3.94 57.52 ± 7.35 32.15± 2.41 27.71 ± 4.35 34.11 ± 9.30 7 39.64 ± 2.56 42.89 ± 4.77 66.10 ±2.15 32.48 ± 1.58 28.79 ± 1.98 41.70 ± 1.52 8 39.30 ± 5.30 48.00 ± 9.4359.27 ± 4.48 30.45 ± 1.83 27.89 ± 1.81 38.14 ± 1.88

Unless otherwise indicated, all numbers expressing quantities ofingredients, properties such as molecular weight, reaction conditions,and so forth used in the specification and claims are to be understoodas being modified in all instances by the term “about.” Accordingly,unless indicated to the contrary, the numerical parameters set forth inthe following specification and attached claims are approximations thatmay vary depending upon the desired properties sought to be obtained bythe present invention. At the very least, and not as an attempt to limitthe application of the doctrine of equivalents to the scope of theclaims, each numerical parameter should at least be construed in lightof the number of reported significant digits and by applying ordinaryrounding techniques. Notwithstanding that the numerical ranges andparameters setting forth the broad scope of the invention areapproximations, the numerical values set forth in the specific examplesare reported as precisely as possible. Any numerical value, however,inherently contains certain errors necessarily resulting from thestandard deviation found in their respective testing measurements.

The terms “a,” “an,” “the” and similar referents used in the context ofdescribing the invention (especially in the context of the followingclaims) are to be construed to cover both the singular and the plural,unless otherwise indicated herein or clearly contradicted by context.Recitation of ranges of values herein is merely intended to serve as ashorthand method of referring individually to each separate valuefalling within the range. Unless otherwise indicated herein, eachindividual value is incorporated into the specification as if it wereindividually recited herein. All methods described herein can beperformed in any suitable order unless otherwise indicated herein orotherwise clearly contradicted by context. The use of any and allexamples, or exemplary language (e.g. “such as”) provided herein isintended merely to better illuminate the invention and does not pose alimitation on the scope of the invention otherwise claimed. No languagein the specification should be construed as indicating any non-claimedelement essential to the practice of the invention.

Groupings of alternative elements or embodiments of the inventiondisclosed herein are not to be construed as limitations. Each groupmember may be referred to and claimed individually or in any combinationwith other members of the group or other elements found herein. It isanticipated that one or more members of a group may be included in, ordeleted from, a group for reasons of convenience and/or patentability.When any such inclusion or deletion occurs, the specification is hereindeemed to contain the group as modified thus fulfilling the writtendescription of all Markush groups used in the appended claims.

Certain embodiments of this invention are described herein, includingthe best mode known to the inventors for carrying out the invention. Ofcourse, variations on those embodiments will become apparent to those ofordinary skill in the art upon reading the foregoing description. Theinventor expects skilled artisans to employ such variations asappropriate, and the inventors intend for the invention to be practicedotherwise than specifically described herein. Accordingly, thisinvention includes all modifications and equivalents of the subjectmatter recited in the claims appended hereto as permitted by applicablelaw. Moreover, any combination of the above-described elements in allpossible variations thereof is encompassed by the invention unlessotherwise indicated herein or otherwise clearly contradicted by context.

Furthermore, numerous references have been made to patents and printedpublications throughout this specification. Each of the above citedreferences and printed publications are individually incorporated byreference herein in their entirety.

In closing, it is to be understood that the embodiments of the inventiondisclosed herein are illustrative of the principles of the presentinvention. Other modifications that may be employed are within the scopeof the invention. Thus, by way of example, but not of limitation,alternative configurations of the present invention may be utilized inaccordance with the teachings herein. Accordingly, the present inventionis not limited to that precisely as shown and described.

What is claimed is:
 1. A medical device comprising ePTFE wherein saidmedical device has a PEG-acrylate coating on at least a portion of saidmedical device surface.
 2. The medical device of claim
 1. wherein saidPEG-acrylate coating is deposited by exposure to at least oneRF-generated plasma.
 3. The medical device of claim 1 wherein saidmedical device is selected from the group consisting of replacementjoints, tubing, vascular grafts, catheters, heart valves, ocular lenses,pacemakers, pacemaker leads and stents.
 4. The medical device of claim 1wherein said PEG-acrylate has the general structureH₂C=CHCO(OCH₂CH₂)_(n)OH, wherein n is an integer between 1 and
 300. 5.The medical device of claim 2 wherein said first RF-generated plasmacomprises an inert gas plasma.
 6. The medical device of claim 5 whereinsaid inert gas plasma is an argon plasma.
 7. The medical device of claim1 wherein said RF-generated plasma is a reactive gas plasma.
 8. Themedical device of claim 7 wherein said reactive gas plasma is an H₂Oplasma.
 9. The medical device of claim 3 wherein said medical device isa vascular stent.
 10. The medical device of claim 3 wherein said medicaldevice is an ablation catheter.